title: Vaccination with Vaxfectin(®) adjuvanted SIV DNA induces long-lasting humoral immune responses able to reduce SIVmac251 Viremia.
abstract: We evaluated the immunogenicity and efficacy of Vaxfectin(®) adjuvanted SIV DNA vaccines in mice and macaques. Vaccination of mice with Vaxfectin(®) adjuvanted SIV gag DNA induced higher humoral immune responses than administration of unadjuvanted DNA, whereas similar levels of cellular immunity were elicited. Vaxfectin(®) adjuvanted SIVmac251 gag and env DNA immunization of rhesus macaques was used to examine magnitude, durability, and efficacy of humoral immunity. Vaccinated macaques elicited potent neutralizing antibodies able to cross-neutralize the heterologous SIVsmE660 Env. We found remarkable durability of Gag and Env humoral responses, sustained during ~2 y of follow-up. The Env-specific antibody responses induced by Vaxfectin(®) adjuvanted env DNA vaccination disseminated into mucosal tissues, as demonstrated by their presence in saliva, including responses to the V1-V2 region, and rectal fluids. The efficacy of the immune responses was evaluated upon intrarectal challenge with low repeated dose SIVmac251. Although 2 of the 3 vaccinees became infected, these animals showed significantly lower peak virus loads and lower chronic viremia than non-immunized infected controls. Thus, Vaxfectin(®) adjuvanted DNA is a promising vaccine approach for inducing potent immune responses able to control the highly pathogenic SIVmac251.
authors.affiliation: Human Retrovirus Pathogenesis Section; Vaccine Branch; Center for Cancer Research; National Cancer Institute; Frederick, MD USA.
authors.forename: Viraj
authors.initials: V
authors.lastname: Kulkarni
authors.affiliation: Human Retrovirus Section; Vaccine Branch; Center for Cancer Research; National Cancer Institute; Frederick, MD USA.
authors.forename: Margherita
authors.initials: M
authors.lastname: Rosati
authors.affiliation: Human Retrovirus Section; Vaccine Branch; Center for Cancer Research; National Cancer Institute; Frederick, MD USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Valentin
authors.affiliation: Human Retrovirus Pathogenesis Section; Vaccine Branch; Center for Cancer Research; National Cancer Institute; Frederick, MD USA.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Jalah
authors.affiliation: Human Retrovirus Pathogenesis Section; Vaccine Branch; Center for Cancer Research; National Cancer Institute; Frederick, MD USA.
authors.forename: Candido
authors.initials: C
authors.lastname: Alicea
authors.affiliation: Institute of Human Virology and Department of Microbiology & Immunology; University of Maryland School of Medicine; Baltimore, MD USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Yu
authors.affiliation: Institute of Human Virology and Department of Microbiology & Immunology; University of Maryland School of Medicine; Baltimore, MD USA.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Duke Human Vaccine Institute; Durham, NC USA.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Shen
authors.affiliation: Duke Human Vaccine Institute; Durham, NC USA.
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.affiliation: Duke Human Vaccine Institute; Durham, NC USA.
authors.forename: Celia
authors.initials: C
authors.lastname: LaBranche
authors.affiliation: Duke Human Vaccine Institute; Durham, NC USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.affiliation: Public Health Research Institute; University of Medicine and Dentistry of New Jersey; Newark, NJ USA.
authors.forename: Carmela
authors.initials: C
authors.lastname: Irene
authors.affiliation: Public Health Research Institute; University of Medicine and Dentistry of New Jersey; Newark, NJ USA.
authors.forename: Rajasekhar
authors.initials: R
authors.lastname: Prattipati
authors.affiliation: Public Health Research Institute; University of Medicine and Dentistry of New Jersey; Newark, NJ USA.
authors.forename: Abraham
authors.initials: A
authors.lastname: Pinter
authors.affiliation: Vical Inc.; Pharmaceutical Sciences; San Diego, CA USA.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Sullivan
authors.affiliation: Human Retrovirus Section; Vaccine Branch; Center for Cancer Research; National Cancer Institute; Frederick, MD USA.
authors.forename: George N
authors.initials: GN
authors.lastname: Pavlakis
authors.affiliation: Human Retrovirus Pathogenesis Section; Vaccine Branch; Center for Cancer Research; National Cancer Institute; Frederick, MD USA.
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Felber
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology; D056724:Immunity, Humoral; D018928:Immunity, Mucosal; D008253:Macaca mulatta; D051379:Mice; D008807:Mice, Inbred BALB C; D010714:Phosphatidylethanolamines / Q000008:administration & dosage*; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014766:Viremia / Q000517:prevention & control*
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D015686:Gene Products, env; D015683:Gene Products, gag; D010714:Phosphatidylethanolamines; D018449:SAIDS Vaccines; D019444:Vaccines, DNA; C460866:vaxfectin
keywords: HIV; Rhesus macaques; SIVmac239; SIVsmE660; V1 and V2 antibodies; adjuvant; antibody; avidity; mucosal immunity; neutralizing antibody; rectal fluid; saliva; systemic immunity